Detecting Bladder Biomarkers for Closed-Loop Neuromodulation: A Technological Review / 대한배뇨장애요실금학회지

Neuromodulation was introduced for patients with poor outcomes from the existing traditional treatment approaches. It is well-established as an alternative, novel treatment option for voiding dysfunction. The current system of neuromodulation uses an open-loop system that only delivers continuous stimulation without considering the patient’s state changes. Though the conventional open-loop system has shown positive clinical results, it can cause problems such as decreased efficacy over time due to neural habituation, higher risk of tissue damage, and lower battery life. Therefore, there is a need for a closed-loop system to overcome the disadvantages of existing systems. The closed-loop neuromodulation includes a system to monitor and stimulate micturition reflex pathways from the lower urinary tract, as well as the central nervous system. In this paper, we reviewed the current technological status to measure biomarker for closed-loop neuromodulation systems for voiding dysfunction.

What caused hemolytic anemia and colicky abdominal pain? Lead!

No abstract available.

Outcome of Video-assisted Thoracoscopic Surgery for Spontaneous Secondary Pneumothorax

BACKGROUND: Conventional treatment (i.e. chest tube insertion and chemical pleurodesis) still remains standard for patients with secondary spontaneous pneumothorax because the risk of surgical bullectomy is deemed high in this subset. However, it has been suggested that surgical treatment using thoracoscopy may expedite postoperative recovery and, thus, may reduce hospital stay. MATERIALS AND METHODS: Retrospective review of 61 patients with secondary spontaneous pneumothorax, who underwent conventional treatment (n=39) or video-assisted thoracoscopic surgery (VATS) (n=22) between January 2007 and December 2009, was performed. Talc was used for chemical pleurodesis in both groups. RESULTS: Hospital stay of conventional treatment group and VATS group was 14.2+/-14.2 days (4~58 days) and 10.6+/-5.8 days (5~32 days), respectively, with statistically significant difference (p=0.033). Recurrence rate of conventional treatment group was also significantly higher (12/39, 30%) compared to VATS group (1/22, 4.5%) (p=0.016). CONCLUSION: In selected patients with secondary spontaneous pneumothorax with continuous air leak or inadequate lung expansion, thoracoscopic surgery with chemical pleurodesis using talc results in shorter hospital stay and lower recurrence rate compared to conventional approach.

Epithelial to Mesenchymal Transition of Mesothelial Cells in Tuberculous Pleurisy

PURPOSE: Tuberculous pleurisy is the most frequent extrapulmonary manifestation of tuberculosis. In spite of adequate treatment, pleural fibrosis is a common complication, but the mechanism has not been elucidated. This study is to determine whether epithelial to mesenchymal transition (EMT) of mesothelial cells occurs in tuberculous pleurisy. MATERIALS AND METHODS: Normal pleural mesothelial cells, isolated from irrigation fluids during operations for primary spontaneous pneumothorax, were characterized by immunofluorescence and reverse transcription polymerase chain reaction (RT-PCR). These cells were treated in vitro with various cytokines, which were produced in the effluents of tuberculous pleurisy. The isolated cells from the effluents of tuberculous pleurisy were analyzed by immunofluorescence and RT-PCR analysis. RESULTS: The isolated cells from the irrigation fluid of primary spontaneous pneumothorax had epithelial characteristics. These cells, with transforming growth factor-beta1 and/or interleukin-1beta treatment, underwent phenotypic transition from epithelial to mesenchymal cells, with the loss of epithelial morphology and reduction in cytokeratin and E-cadherin expression. Effluent analysis from tuberculous pleurisy using immunofluorescence and RT-PCR demonstrated two phenotypes that showed mesenchymal characteristics and both epithelial & mesencymal characteristics. CONCLUSION: Our results suggest that pleural mesothelial cells in tuberculous pleurisy have been implicated in pleural fibrosis through EMT.

Outcomes of Sleeve Lobectomy versus Pneumonectomy for Lung Cancer

BACKGROUND: Sleeve lobectomy for lung cancer in close proximity to or involving the carina is widely accepted. Operative morbidity and mortality rates, recurrence, and survival rates have varied considerably across studies. MATERIALS AND METHODS: From March of 2005 to July of 2010, sleeve lobectomy was performed in 19 patients and pneumonectomy was performed in 20 patients. In this paper, the results of sleeve lobectomy and pneumonectomy for patients with lung cancer will be compared and evaluated. RESULTS: There were no postoperative complications in either group, but there was one mortality in the pneumonectomy group. There was better preservation of pulmonary function in the sleeve lobectomy group than the pneumonectomy group (p=0.066 in FVC, p=0.019 in FEV1). The 3-year survival rates were 46.7% in the sleeve lobectomy group and 54.5% in the pneumonectomy group (p=0.505). The 3-year disease-free survival rates were 38% in the sleeve lobectomy group and 45.8% in the pneumonectomy group (p=0.200). CONCLUSION: Sleeve lobectomy for lung cancer showed low mortality, low bronchial anastomotic complication rates, and good preservation of pulmonary function.

Transatrial Repair of Post-infarction Posterior Ventricular Septal Rupture

Ventricular septal rupture (VSR) is a rare but lethal complication of myocardial infarction. The event occurs 2~8 days after an infarction and often precipitates cardiogenic shock. Post myocardial infarction VSR is known for difficult to repair. Especially, Transmural myocardial infarction involved in the posterior VSD area, exposure of the affected site is difficult and postoperative mortality rate is high. We have experienced a case of a 75-year-old female patient who suffered posterior VSD due to acute myocardial infarction, and attained good result by approaching the lesion through right atrial incision and repaired the defect by using patch closure technique.

A Case of Acinar Cell Carcinoma of Pancreas, Manifested by Subcutaneous Nodule as Initial Clinical Symptom / 대한소화기학회지

Pancreas acinar cell carcinoma (ACC) accounts for only 1-2% of pancreatic exocrine malignant tumor. The symptoms of patients with ACC are usually non-specific, for example the anorexia and weight loss. Patients may develop Schmid's triad including subcutaneous fat necrosis, polyarthritis, and eosinophilia. We reported a case of ACC which was manifested by subcutaneous nodule as initial clinical symptom. To our knowledge, this is the first reported case of ACC presenting as subcutaneous fat necrosis in Korea.

Serum Uric Acid as a Predictor for the Development of Nonalcoholic Fatty Liver Disease in Apparently Healthy Subjects: A 5-Year Retrospective Cohort Study

BACKGROUND/AIMS: This study evaluated the relationship between hyperuricemia and nonalcoholic fatty liver disease (NAFLD) by comparing the incidence rates of NAFLD in relation to serum uric acid levels in apparently healthy subjects during a 5-year period. METHODS: Among 15,638 healthy Korean subjects who participated in a health-screening program in 2003 and 2008, respectively, 4954 subjects without other risk factors were enrolled in this study. We compared the incidence rates of NAFLD in 2008 with respect to baseline uric acid levels. RESULTS: In 2003, serum uric acid levels were categorized into the following quartiles: 0.6-3.9, 3.9-4.8, 4.8-5.9, and 5.9-12.6 mg/dL. The incidence of NAFLD in 2008 increased with the level of baseline uric acid (5.6%, 9.8%, 16.2%, and 20.9%, respectively; p<0.05). Multiple logistic regression analysis demonstrated that hyperuricemia was associated with the development of NAFLD. When compared to the subjects in quartile 1, the odds ratio (OR) for the incidence of NAFLD for quartiles 2, 3, and 4 were 1.53 (95% confidence interval [CI], 1.09-2.16; p=0.014], 1.69 (95% CI, 1.17-2.44; p=0.005), and 1.84 (95% CI, 1.25-2.71; p=0.002), respectively. CONCLUSIONS: High serum uric acid levels appear to be associated with an increased risk of the development of NAFLD.

The Clinical Results of Surgical Treatment for Sternoclavicualr Septic Arthritis / 대한흉부외과학회지

BACKGROUND: Sternoclavicular septic arthritis manifests serious complications such as abscess, osteomyelitis, mediastinitis and empyema; therefore, a prompt diagnosis and appropriate treatment are necessary. MATERIAL AND METHOD: The treatment results of eight patients with sternoclavicular septic arthritis and who had been surgically treated at our institutions between September 2005 and July 2008 were retrospectively reviewed. The surgical treatment they underwent was en bloc resection, including partial resection of the sternum, the clavicular head and the 1st rib. RESULT: The patients ranged in age from 40 to 74 years with an average of 55.1+/-10.3 years. Five were men and three were women. There were 6 patients with spontaneous sternoclavicular septic arthritis and 2 patients had their condition induced by central venous catheters. The pathogens isolated from the patients' blood and wounds were MRSA (3), Streptococcus intermedius (1), Streptococcus agalactiae (1) and Pseudomonas luteola (1). One patient expired from aggravation of preoperative sepsis on POD 31. CONCLUSION: The life-threatening complications from sternoclavicular septic arthritis can progress and lead to death unless appropriate treatment is administered. A prompt diagnosis, appropriate antibiotics therapy and effective surgical treatment such as radical en bloc resection can reduce the morbidity and mortality of this malady.

Video-Assisted Thoracic Surgery Lobectomy: Experience with 36 Cases / 대한흉부외과학회지

BACKGROUND: Many video-assisted thoracic surgery (VATS) lobectomies are performed as a potential alternative to thoracotomy despite the controversy about the safety and the associated morbidity/mortality rates. MATERIAL AND METHOD: Between November 2006 and August 2008, we performed 87 lobectomies (VATS 36, Thoracotomy 51) and we retrospectively reviewed the surgical treatment results. A VATS lobectomy was performed by a 4~5 cm thoracotomy without rib spreading and this included anatomic hilar dissection, individual vessel and bronchus stapling and lymph node dissection. RESULT: We studied 52 male and 35 female patients whose age ranged from 6 to 79 (average age: 59.8+/-15.0 years). The cases were diagnosed with lung cancer (66) (SQC 24, ADC 38, others 4), pulmonary metastasis (2), carcinoid (2) and benign diseases (17). There was no intraoperative death. Postoperative complications were seen in 5 (15.6%) VATS and 33 (64.7%) thoracotomies, and perioperative death caused by adult respiratory distress syndrome occurred in 1 (2.8%) VATS and 3 (5.9%) thoracotomies. Three patients underwent conversion to thoracotomy (8.3%). The mean time to chest tube removal was 6 days for VATS and 9.4 days for thoracotomy (p<0.001), and the mean length of the hospital stay was 8 days for VATS and 12.8 days for thoracotomy (p<0.001). CONCLUSION: VATS lobectomy can be performed safely with low morbidity/mortality rates. Furthermore, all the patients benefited from earlier postoperative rehabilitation and less pain and they were candidates for an earlier return to normal activities.

Catamenial Hemoptysis Treated by Video-assisted Thoracoscopic Surgery / 결핵및호흡기질환

Catamenial hemoptysis is a rare condition that's characterized by recurrent hemoptysis occurring in association with menstruation, and this is associated with the presence of intrapulmonary or endobronchial endometrial tissue. The diagnosis of pulmonary endometriosis can be made according to a typical clinical history and with exclusion of other causes of recurrent hemoptysis. Treatment of pulmonary endometriosis can be medical or surgical; however, the optimal management of this condition is still a matter of debate. Medical therapy may be problematic, due to recurrence of symptoms despite hormonal ablation, and adverse effects from long-term hormone therapy can also be a problem. We report here on a case of pulmonary endometriosis in a 23-year-old woman who presented with hemoptysis that occurred during the first 3 days of menstruation, and this happened over a 4 month period. She was successfully treated by video-assisted thoracoscopic surgery (VATS). No more hemoptysis was noted during 12 months of follow-up.

The Clinical Application and Results of Palliative Damus-Kaye-Stansel Procedure / 대한흉부외과학회지

BACKGROUND: The Damus-Kaye-Stansel (DKS) procedure is a proximal MPA-ascending aorta anastomosis used to relieve systemic ventricular outflow tract obstructions (SVOTO) and pulmonary hypertension. The purpose of this study was to review the indications and outcomes of the DKS procedure, including the DKS pathway and semilunar valve function. MATERIAL AND METHOD: A retrospective review of 28 patients who underwent a DKS procedure between May 1994 and April 2006 was performed. The median age at operation was 5.3 months (13 days~38.1 months) and body weight was 5.0 kg (2.9~13.5 kg). Preoperative pressure gradients were 25.3+/-15.7 mmHg (10~60 mmHg). Eighteen patients underwent a preliminary pulmonary artery banding as an initial palliation. Preoperative main diagnoses were double outlet right ventricle in 9 patients, double inlet left ventricle with ventriculoarterial discordance in 6, another functional univentricular heart in 5, Criss-cross heart in 4, complete atrioventricular septal defect in 3, and hypoplastic left heart variant in 1. DKS techniques included end-to-side anastomosis with patch augmentation in 14 patients, classical end-to-side anastomosis in 6, Lamberti method (double-barrel) in 3, and others in 5. The bidirectional cavopulmonary shunt and Fontan procedure were concomitantly performed in 6 and 2 patients, respectively. RESULT: There were 4 hospital deaths (14.3%), and 3 late deaths (12.5%) with a follow-up duration of 62.7+/-38.9 months (3.3~128.1 months). Kaplan-Meier estimated actuarial survival was 71.9%+/-9.3% at 10 years. Multivariate analysis showed right ventricle type single ventricle (hazard ratio=13.960, p=0.004) and the DKS procedure as initial operation (hazard ratio=6.767, p=0.042) as significant mortality risk factors. Four patients underwent staged biventricular repair and 13 received Fontan completion. No SVOTO was detected after the procedure by either cardiac catheterization or echocardiography except in one patient. There was no semiulnar valve regurgitation (>Gr II) or semilunar valve-related reoperation, but one patient (3.6%) who underwent classical end-to-side anastomosis needed reoperation for pulmonary artery stenosis caused by compression of the enlarged DKS pathway. The freedom from reoperation for the DKS pathway and semilunar valve was 87.5% at 10 years after operation. CONCLUSION: The DKS procedure can improve the management of SVOTO, and facilitate the selected patients who are high risk for biventricular repair just after birth to undergo successful staged biventricular repair. Preliminary pulmonary artery banding is a safe and effective procedure that improves the likelihood of successful DKS by decreasing pulmonary vascular resistance. The long-term outcome of the DKS procedure for semilunar valve function, DKS pathway, and relief of SVOTO is satisfactory.

The Role of GADD45beta in Acute Myocardial Injury / 대한흉부외과학회지

BACKGROUND: A critical shortage of donor organs has necessitated an investigation of new strategies to increase the availability of additional organs available for human transplantation. We investigated the amount of apoptosis and expression of GADD45beta in two groups, a GADD45beta-transfected group and untransfected group. MATERIAL AND METHOD: The experimental groups consist of a control group (normal H9C2 cell line) and GADD45beta-transfected group. After injury of the each group, we evaluated the expression of GADD45beta and the level of apoptosis in each group. RESULT: There was a significant increase in the expression of GADD45beta in the GADD45beta-transfected group at 1 hour, 2 hours, and 3 hours after stimuli as compared with the control group. The amount of cardiac myoblast cell line apoptosis was significantly lower in the GADD45beta-transfected group as compared with the control group. The concentration of annexin in the GADD45beta-transfected group was significantly lower than that of the control group after cell injury. CONCLUSION: Transfection of a rat myoblast cell line with the GADD45beta gene results in decreased susceptibility to cell injury of human serum.

Surgical Treatment for Descending Necrotizing Mediastinitis / 대한흉부외과학회지

BACKGROUND: Descending necrotizing mediastinitis (DNM) is a serious disease originating in odontogenic or oropharyngeal infection with high mortality despite adequate antibiotics and aggressive surgery. We analyzed results of treatment for DNM. MATERIAL AND METHOD: We studied 8 cases diagnosed as DNM from 1998 to 2007. All patients received emergent surgical drainage and debridement with broad spectrum antibiotics just after diagnosis. Antibiotics were changed after bacterial susceptibility testing. The surgical approach included 2 cases of cervicotomy, 6 cases of cervicotomy, and a thoracotomy. RESULT: The interval between symptom onset and hospitalization was 4.6+/-1.8 days (1~9 day). DNM originated in 4 cases of odontogenic infection (50%), 2 cases of oropharyngeal infection (25%), and 2 cases of unknown origin (25%). Causative organisms were found in 6 cases; Streptococcus in 4 cases, Staphylococcus in 1 case, and Klebsiella in 1 case. The Endo DNM classification was type I (2 cases), IIA (3 cases), and IIB (3 cases). The incidence of thoracotomy was 75%. The surgical mortality rate was 25% (2/8). The cause of death was multiple organ failure caused by septic shock. All mortality cases received only cervicotomy and aggravated infections after initial drainage. CONCLUSION: Early diagnosis, immediate surgical drainage, and adequate antibiotics, including covered anaerobes, are required. Thoracotomy should be performed with cervicotomy even for localized DNM.

Clinical Results and Risk Factor Analysis of Surgical Treatment for Esophageal Perforation / 대한흉부외과학회지

BACKGROUND: Esophageal perforation is an emergency that requires early diagnosis and effective treatment. A delay in diagnosis and treatment significantly increases morbidity and mortality. MATERIAL AND METHOD: Thirty-seven patients with esophageal perforation were surgically treated at our institutions between January 1990 and December 2006. We retrospectively reviewed the results of surgical treatment for esophageal perforation to understand the risk factors affecting survival in patients. RESULT: Patients ranged in age from 21 to 87 years, with an average age of 52.7+/-16.98 years. Thirty-one of the patients were men and six were women. There were 23 patients (62%) with spontaneous perforations, 10 patients (27%) with a traumatic perforation, and 4 patients (11%) with an iatrogenic perforation. The site of esophageal perforation was the cervical esophagus in 5 patients, the thoracic esophagus in 31 patients, and the abdominal esophagus in one patient. Twenty-nine patients underwent primary closure of the perforation and five patients had T-tube drainage. Exclusion-diversion procedures were performed in two patients and an esophagectomy was performed in one patient. There were six cases of mortality (16.22%) and 25 cases of postoperative complications in 15 patients (40.5%). Patients that were treated later than 24 hours after detection of the perforation showed a statistically significant high morbidity and mortality rate (p<0.05). CONCLUSION: The most important risk factor of esophageal perforation was the time interval between detection of the perforation and the initiation of treatment. A prompt diagnosis and effective treatment are necessary to decrease morbidity and mortality.

Dosage Adjustment before and after Warfarin - Rifampin Combination Therapy / 대한흉부외과학회지

BACKGROUND: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin - rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. MATERIAL AND METHOD: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan 1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). RESULT: The average INR of all the patient before rifampin administration was 2.25+/-0.52 (mean+/-SD), and that value for the first 100 days after rifampin administration was 1.98+/-0.28. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was 2.19+/-0.34, and the value after rifampin cessation was 2.49+/-0.43. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. CONCLUSION: The warfarin dose adjustment equation of before and after warfarin - rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

A Case of Thyroid Cancer Combined with Pulmonary Sarcoidosis / 결핵및호흡기질환

Sarcoidosis is a systemic granulomatous disease that primarily affects the lung and lymphatic system of the body. Since Brincker first noted a statistically significant increase of malignant tumors among sarcoidosis patients, there have been several reports on simultaneously developed sarcoidosis and malignancy. A 30-year-old man was admitted to our hospital because of multiple enlarged mediastinal lymph nodes. The patient had been well until approximately 10 days before admission, when he developed a cough. Chest X-ray and computed tomography (CT) of the chest that were performed at the outpatient department revealed multiple enlarged mediastinal lymph nodes. Cervical lymph node biopsy revealed both non-caseating granuloma and metastatic papillary carcinoma, whereas the mediastinal lymph node showed only non-caseating granuloma. The thyroid gland surgical specimen showed papillary carcinoma. We report here on a case of a 30-year-old man who had sarcoidosis and thyroid cancer, and we include a review of the literature.

A Trial of Aerosolized Colistin for the Treatment of Nosocomial Pneumonia due to Multidrug-resistant Acinetobacter baumannii / 결핵및호흡기질환

BACKGROUND: Recently, multidrug-resistant (MDR) A. baumannii has been implicated for a significant proportion of nosocominal pneumonia in many intensive care units (ICUs), and its acquisition may increase mortality and the length of stay in the ICU. Aerosolized colistin has been successfully used in patients with cystic fibrosis, but there is a lack of data regarding the use of aerosolized colistin in patients with nosocomial pneumonia. METHODS: We conducted the present study to assess the effectiveness of aerosolized colistin for the treatment of MDR A. baumannii nosocomial pneumonia. We retrospectively reviewed the medical records of 10 patients who had been hospitalized in the medical ICU and had received aerosolized colistin as a therapy for MDR A. baumannii pneumonia. RESULTS: The mean duration of aerosolized colistin therapy was 12.7+/-2.4 days. Nine (90%) of 10 patients showed a favorable response to the therapy. Follow-up cultures were available for all patients, and the responsible pathogen was completely eradicated. One patient suffered from bronchospasm, which resolved after treatment with nebulized salbutamol. CONCLUSION: Our results corroborate previous reports that aerosolized colistin may be an effective and safe choice for the treatment of nosocomial pneumonia caused by MDR A. baumannii. Larger prospective controlled clinical studies are warranted to validate further the effectiveness and safety of aerosolized colistin therapy.

A Case of Bronchus-Associated Lymphoid Tissue(BALT) Lymphoma Treated with Lobectomy / 결핵및호흡기질환

The bronchus-asociated lymphoid tissue(BALT) lymphoma is a low-grade primary malignant lymphoma that originates from bronchus associated lymphoid tissue. A 67-year-old woman was admitted for evaluation of cough, sputum, rhinorrhea which had persisted for one month. Physical examination showed decreased breathing sound on the left upper lung field. High resolution chest computed tomography demonstrated consolidation which showed air-bronchogram and surrounding ground glass opacity in left upper lobe. These findings implicated inactive tuberculosis, organizing pneumonia, or bronchiolo-alveolar carcinoma. The histologic findings from percutaneous needle aspiration biopsy revealed aggregated atypical small lymphoid cells with lymphoepithelial lesions. With immunohistochemical staining, the atypical lymphoid cells reacted positively with CD 20 antibody and negatively with CD 3 antibody. Thus, we could diagnosed her as a patient with BALT lymphoma. After left upper lobectomy, she has been well without recurrence of the disease for 14 months. In this country of Republic of Korea, it was the 1st case of BALT lymphoma surgically treated when histological diagnosis had been done. Based on this case, we wanted to demonstrate the importance of early histological diagnosis and treatment of BALT lymphoma.

Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen

Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -alpha and -beta, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 micrometer). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-alpha and ER-beta compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-beta estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-kappaB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-kappaB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-kappaB pathway may be more closely involved in BPA-induced neuronal toxicity.